The bifurcation 1-stent strategy is the preferred approach in treating coronary bifurcation lesions with drug-eluting stents (DES), because the bifurcation 2-stent strategy has been associated with worse clinical outcomes compared with the 1-stent strategy (1). However, it is important to remember that the notion was derived from comparison between patients who could be treated with the 1-stent strategy and those who needed the 2-stent strategy. A 2-stent approach is required when treating true bifurcation lesions with a side branch subtending a large area of myocardium. This is particularly true when the lesion in the side branch is long. Therefore, there is an obvious need for detailed evaluation of the outcomes of bifurcation stenting with 2 stents and for development of the optimal 2-stent strategy.

In this issue of JACC: Cardiovascular Interventions, Song et al. (2) report the predictors of target vessel failure after bifurcation 2-stenting in a patient-level pooled analysis of the Korean Bifurcation Pooled Cohort. The investigators should be congratulated on their analysis of the largest ever study population, which underwent bifurcation 2-stenting with 3-year follow-up. The independent predictors included angiographic factors, such as left main coronary artery (LMCA) bifurcation and high SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, and device and procedural factors, such as the use of second-generation DES, the use of a noncompliant balloon, and final kissing balloon, as well as the clinical factor of diabetes.

The present study’s results are consistent with our previous report suggesting that the risk for target lesion revascularization (TLR) after the bifurcation 2-stent approach was significantly higher in LMCA bifurcations than in left anterior descending coronary artery bifurcations (3). Excess TLR risk of bifurcation 2-stenting relative to bifurcation 1-stenting is particularly relevant in patients undergoing LMCA stenting, because the need for 2 stents and the potential prognostic impact of TLR might also be greater in LMCA bifurcations than in left anterior descending coronary artery bifurcations. LMCA stenting has been widely used as an alternative to coronary artery bypass grafting (CABG) since the publication of 2 randomized controlled trials comparing LMCA stenting with CABG that demonstrated comparable 5-year clinical outcomes, albeit with a higher rate of repeat coronary revascularization after LMCA stenting (4,5). However, in patients with LMCA disease who are expected to need the 2-stent approach, CABG may remain the preferred revascularization strategy in the heart team’s discussion. Every effort should be made to improve clinical outcomes after LMCA bifurcation 2-stenting to expand the indication for LMCA stenting safely and effectively.

In the present study, the use of second-generation DES was associated with markedly lower risk for target vessel failure (adjusted hazard ratio: 0.26; 95% confidence interval: 0.12 to 0.57). The finding is gratifying, because we are now almost exclusively using second-generation DES. However, in our meta-analysis of 14 randomized controlled trials comparing a second-generation DES (everolimus-eluting stent) with a first-generation DES (sirolimus-eluting stent) in patients with a wide range of coronary artery disease, the pooled odds ratio of the everolimus-eluting stent relative to the sirolimus-eluting stent for the risk for TLR was only 0.84 (6). In the present study, the vast majority of patients were included from a dedicated bifurcation stenting registry, while 265 patients with second-generation DES were derived from 2 “all-comers” registries of second-generation DES. Caution is warranted regarding the possibility that the magnitude of the favorable effect due to the second-generation DES might be overestimated because of differences in the design of the original registries included in the pooled cohort, although the magnitude of improvement with second-generation DES might be greater for complex stenting, such as bifurcation 2-stenting, than for simple stenting. The impact of second-generation DES on the outcomes of LMCA stenting will be clarified by the ongoing EXCEL (Evaluation of XIENCE Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization) trial, the largest dedicated trial comparing LMCA stenting using a second-generation DES (everolimus-eluting stent) with CABG in patients with SYNTAX scores ≤32. If the EXCEL trial demonstrates noninferiority of LMCA stenting to CABG, further penetration of LMCA stenting in real-world clinical practice can be expected.

Even after the EXCEL trial, the relatively poor outcomes of LMCA bifurcation 2-stenting will remain the Achilles’ heel of LMCA stenting, which consist mainly of restenosis of the ostial left circumflex coronary artery and stent thrombosis (1). The greatest limitation in research on LMCA bifurcation 2-stenting is that each study does not include a sufficient number of patients with bifurcation 2-stenting to compare outcomes among various bifurcation 2-stent techniques. There also is wide variation in bifurcation anatomy in terms of bifurcation angle and the relative vessel sizes of the LMCA, left anterior descending coronary artery, and left circumflex coronary artery. Furthermore, it is possible that some second-generation DES are more suitable than others for LMCA bifurcation 2-stenting. Therefore, there are many variables influencing the outcomes of LMCA bifurcation 2-stenting, despite the limited number of patients included in each study.

Nevertheless, the optimal LMCA bifurcation 2-stenting strategy should be defined to make LMCA stenting safer and more efficacious. The first step moving forward would be to launch a large retrospective registry evaluating the outcomes of LMCA bifurcation 2-stenting. There are several prerequisites to design a clinically relevant registry. First, the types of DES should be the second-generation DES that are currently available. Second, as many centers as possible with good experience in LMCA bifurcation 2-stenting should be invited to participate. The number of participating centers is important not only for collecting a large number of patients but also for adjusting the preference of a particular center for a particular bifurcation 2-stent technique. Third, patient enrollment should be consecutive. Forth, clinical, angiographic (both qualitative and quantitative), and procedural data should be collected as extensively as possible. A dedicated LMCA bifurcation 2-stenting registry designed in this fashion would overcome the limitations associated with the ad hoc pooling of different types of registries. If a hypothesis is produced suggesting better outcomes of a particular bifurcation 2-stenting strategy for a particular bifurcation anatomy, a prospective randomized study should be conducted to establish the optimal LMCA bifurcation 2-stenting strategy.

Finally, despite the importance of establishing the optimal LMCA bifurcation 2-stenting strategy, it should be noted that patients who need LMCA bifurcation 2-stenting often have complex disease in coronary artery territories other than the LMCA (1). In patients with complex triple-vessel coronary artery disease, CABG was associated with better 5-year survival than stenting (4). Even if LMCA bifurcation could be effectively treated, many of the patients who need LMCA bifurcation 2-stenting would currently be more suited for CABG than for stenting, because of the presence of complex disease outside the LMCA. Therefore, efforts to establish the optimal LMCA bifurcation 2-stenting strategy should be complemented by endeavors to improve the outcomes of coronary stenting in patients with complex triple-vessel coronary artery disease.

Footnotes

↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.

Dr. Kimura has reported that he has no relationships relevant to the contents of this paper to disclose.

(2011) Different incidence of target-lesion revascularization after bifurcation two-stent approach with sirolimus-eluting stent between left main coronary artery bifurcation and left anterior descending coronary artery bifurcation. EuroIntervention7:796–804.